Department of Fundamental Neurosciences, University of Lausanne, 1005 Lausanne, Switzerland.
Department of Pharmacology and Physiology, University of Rome Sapienza, 00185 Rome, Italy.
Int J Mol Sci. 2022 Apr 16;23(8):4412. doi: 10.3390/ijms23084412.
The 22q11 deletion syndrome (DS) is the most common microdeletion syndrome in humans and gives a high probability of developing psychiatric disorders. Synaptic and neuronal malfunctions appear to be at the core of the symptoms presented by patients. In fact, it has long been suggested that the behavioural and cognitive impairments observed in 22q11DS are probably due to alterations in the mechanisms regulating synaptic function and plasticity. Often, synaptic changes are related to structural and functional changes observed in patients with cognitive dysfunctions, therefore suggesting that synaptic plasticity has a crucial role in the pathophysiology of the syndrome. Most interestingly, among the genes deleted in 22q11DS, six encode for mitochondrial proteins that, in mouse models, are highly expressed just after birth, when active synaptogenesis occurs, therefore indicating that mitochondrial processes are strictly related to synapse formation and maintenance of a correct synaptic signalling. Because correct synaptic functioning, not only requires correct neuronal function and metabolism, but also needs the active contribution of astrocytes, we summarize in this review recent studies showing the involvement of synaptic plasticity in the pathophysiology of 22q11DS and we discuss the relevance of mitochondria in these processes and the possible involvement of astrocytes.
22q11 缺失综合征（DS）是人类最常见的微缺失综合征，发生精神疾病的概率较高。突触和神经元功能障碍似乎是患者出现症状的核心。事实上，人们早就认为，22q11DS 中观察到的行为和认知障碍可能是由于调节突触功能和可塑性的机制发生改变所致。通常，突触变化与认知功能障碍患者观察到的结构和功能变化有关，因此表明突触可塑性在该综合征的病理生理学中起着关键作用。最有趣的是，在 22q11DS 缺失的基因中，有 6 个编码线粒体蛋白，在小鼠模型中，这些蛋白在出生后立即大量表达，此时正是活跃的突触发生时，这表明线粒体过程与突触形成和维持正确的突触信号传递密切相关。因为正确的突触功能不仅需要正确的神经元功能和代谢，还需要星形胶质细胞的积极贡献，所以我们在这篇综述中总结了最近的研究，这些研究表明突触可塑性参与了 22q11DS 的病理生理学过程，并讨论了线粒体在这些过程中的相关性以及星形胶质细胞的可能参与。
